Lots of considerations when evaluating the FujiLAM assay - Author's reply.

We thank Alberto Garcia-Basteiro and colleagues for their response to our research Article on the novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries.1Huerga H Bastard M Lubega AV et al.Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study.Lancet Glob Health. 2023; 11: e126-e135Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar The evaluation of the inter-lot and intra-lot variability in diagnostic accuracy of an assay is usually not part of late-stage clinical studies but should be assessed during quality control by manufacturers. In this case, we were informed by FIND and the assay manufacturer about inter-lot variability of FujiLAM (Fujifilm, Tokyo, Japan) after our study was completed. Following discussions with our scientific advisory board, we added post-hoc analyses of diagnostic accuracy by test lot. Given the importance of the lot-to-lot variability, we presented pooled and by lot accuracy estimates as part of the main study results. A similar approach presenting pooled and by lot diagnostic accuracy estimates has been used by the FujiLAM study consortium.2Székely R Sossen B Mukoka M et al.Multicentre accuracy trial of FUJIFILM SILVAMP TB LAM test in people with HIV reveals lot variability.medRxiv. 2022; (published online Sept 9.) (preprint).https://doi.org/10.1101/2022.09.07.22278961Google Scholar Regarding the implications of these findings, as stated in the summary and discussion of our Article, this version of the FujiLAM assay cannot be recommended for clinical use until the problem of inter-lot variability is resolved. We believe that sharing the results from a large and rigorous prospective clinical study is important to inform the scientific community, policy makers, end-users, and programme managers on the performance of an assay that has been considered a promising urine-based point-of-care test.3Broger T Nicol MP Székely R et al.Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: a meta-analysis of individual in- and outpatient data.PLoS Med. 2020; 17e1003113Crossref PubMed Scopus (44) Google Scholar We also hope that these data will be used by the manufacturer to inform root-cause analysis, identify solutions, and communicate these to key stakeholders. We think that providing data in a transparent manner will not damage confidence in the currently recommended Alere Determine TB-LAM Ag test (Abbott, Waltham, MA, USA). Notable reasons for low uptake of this test are related to challenges with access, budget limitations, and difficulties in obtaining regulatory agency approvals.4Singhroy DN MacLean E Kohli M et al.Adoption and uptake of the lateral flow urine LAM test in countries with high tuberculosis and HIV/AIDS burden: current landscape and barriers.Gates Open Res. 2020; 4: 24Crossref PubMed Google Scholar We believe that our conclusion is clear enough to prevent any false hope. We also think that we have an ethical obligation towards the study participants to publish these data. Notably, the results on inter-lot variability reported by our group and others raise an important question on whether inter-lot and intra-lot variability should be systematically assessed as part of clinical diagnostic studies, and at which stage it is most appropriate to evaluate this. These considerations should be discussed when providing updated guidance for the evaluation of new diagnostics.5Denkinger CM Schumacher SG Gilpin C et al.Guidance for the evaluation of tuberculosis diagnostics that meet the World Health Organization (WHO) target product profiles: an introduction to WHO process and study design principles.J Infect Dis. 2019; 220: S91-S98Crossref PubMed Scopus (17) Google Scholar Sputum-free point-of-care diagnostic tests for tuberculosis remain urgently needed. Despite these disappointing results for this version of the FujiLAM assay, we hope that research to develop more sensitive LAM-based point-of-care assays will continue.6Sossen B Meintjes G Development of accurate non-sputum-based diagnostic tests for tuberculosis: an ongoing challenge.Lancet Glob Health. 2023; 11: e16-e17Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar We declare no competing interests. Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy studyNext-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use. Full-Text PDF Open AccessLots of considerations when evaluating the FujiLAM assayPoint-of-care non-sputum-based tests for tuberculosis are an international research priority,1 particularly for populations for whom bacteriological confirmation is difficult, such as children or people who are immunocompromised and living with HIV. The urine-based Alere Determine TB LAM Ag (Abbott, Waltham, MA, USA) test partly meets these criteria, however, the test has important shortcomings that must be overcome. Full-Text PDF Open Access